Towards Inference of Fitness Landscapes in Human Cancer
summary
Introduces three concrete tools and results: X-seq integrates mutations with gene expression across ~3,000 TCGA tumors (≈500,000 mutations) and flags ~30 novel cis tumor‑suppressor candidates and ~89 trans candidates, showing ~25% of β‑catenin‑mutant endometrial tumors lack expected pathway activation. Hyclone is a Bayesian deconvolution of allele fractions and copy number that clusters mutations into clones and validates on engineered mixes. Serial patient samples and xenografts reveal reproducible selective sweeps of rare clones versus preserved architecture in treatment relapse.
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chapters (11)
- 0:00Introduction to cancer evolution
- 0:24Genotype to phenotype modeling
- 7:05Identifying tumor suppressors
- 11:21Measuring population dynamics
- 14:23Clonal reconstruction with PiClone
- 16:27Follicular lymphoma case study
- 21:07Models of disease progression
- 22:38Experimental validation
- 26:04Microenvironmental influences
- 30:20Conclusion and acknowledgments
- 31:44Q&A session